More than 90% of the world population is persistently infected with several herpesviruses. Kaposi's[unreadable] sarcoma-associated herpesvirus (KSHV) can establish persistent infection in the oral cavity and can be[unreadable] transmitted orally. KSHV infection manifests in AIDS patients and leads to several lymphoproliferative[unreadable] diseases as well as Kaposi's sarcoma. Although the host cells and the immune system have evolved[unreadable] mechanisms to control herpesviral infections, herpesviruses have also developed strategies to evade and/or[unreadable] antagonize them. Herpesviruses employ multiple viral genes to achieve precise gene expression control and[unreadable] to counteract the host immune system, both of which are essential to establish, maintain, and reactivate from[unreadable] latency. The successful transition between latency and lytic replication is critical for viral persistence in the[unreadable] host. It has not been clearly understood about how the virus regulates its own expression and deregulates[unreadable] cellular transcription to efficiently replicate and evade immune responses.[unreadable] To understand the mechanisms of KSHV persistence, concentrated on at the level of gene expression[unreadable] regulation and immune evasion, four laboratories in California join forces. The following four projects will be[unreadable] primarily addressed: 1) the mechanism of inhibition on type inhibiting interferon production by KSHV ORF36[unreadable] (project leader: Ren Sun, UCLA); 2) the transcriptional regulatory role of ORF36 as the sole viral kinase of[unreadable] KSHV (project leader: Hsing-Jien Kung, UC Davis); 3) the mechanism underlying two KSHV-encoded[unreadable] modulators (ORF10 and ORF45) of innate immune pathways (Project leader, Don Ganem, UCSF); 4)[unreadable] development of develop a non-human primate model for the KSHV persistent infection of KSHV to determine[unreadable] the immune evasive role of ORF10, ORF36, K-bZIPPRF45 and K5K3 during viral infection in vivo (Project[unreadable] leader: Jae Jung, Harvard/USC).[unreadable] Public Relevance[unreadable] There are extensive interactions among projects, which generate synergy towards one common theme: the[unreadable] virus-host interactions underlying the persistent infection of KSHV. These collaborative activities are[unreadable] facilitated by a Coordination Administration Core. Accomplishing these goals will provide new insight and[unreadable] opportunities to develop novel therapeutic approaches against persistent herpesviral infection and[unreadable] associated diseases. Further, the collaboration stimulated by this program project will not only promote[unreadable] researches outlined in this proposal, but also facilitate joint researches in other aspects of KSHV biology and[unreadable] cultivation of new generation of scientists for multidisciplinary research in the herpesvirology field.